Biology subjects

Pueschel, K.

Publications and source records attributed to Pueschel, K..

4 recordsLinked to original sources

bioRxiv2026

Diffusion tensor imaging of whole human brains during long-term formaldehyde fixation: Temporal evolution of diffusion parameters, post-mortem conditions, and dependence on tissue structure

Purpose: Post-mortem Diffusion Magnetic Resonance Imaging (dMRI) findings on fixation-related changes in diffusion tensor imaging (DTI) parameters remain inconsistent, partly due to lower diffusion weighting and sparse early-fixation sampling. This study investigated how post-mortem tissue condition, fixation progression, and diffusion weighting shape DTI parameters in whole human brains, including whether an ex-vivo-adjusted protocol also suits in-situ and early fixation measurements. Methods: Six neurologically healthy whole human brains (post-mortem interval (PMI) 12 - 24 h) were scanned across tissue conditions, including an in-vivo reference cohort. Five brains were scanned longitudinally through immersion fixation (0 - 150 days), yielding 175 datasets with dense early sampling. Diffusion measurements at b-values 1000 - 4000 s/mm2 assessed the influence of diffusion weighting on DTI parameters. Analyses covered multiple white- and gray-matter regions and within white matter stratification by fiber orientation dispersion ({kappa}). Results: The largest mean diffusivity (MD) shift occurred between in-vivo and in-situ, whereas fractional anisotropy (FA) changed most strongly during early fixation. During immersion fixation, MD showed reproducible monoexponential saturation, while FA was heterogeneous across brains. PMI, {kappa}, and regional anatomy explained substantial FA heterogeneity across specimens. Qualitatively, the fixationrelated changes matched across diffusion weightings, but precision across specimens was highest at b-value 4000 s/mm2. Conclusion: During fixation, MD is a robust temporal marker, whereas FA requires microstructureaware interpretation. Diffusion weighting modulates how clearly fixation effects can be resolved, but the same qualitative fixation dynamics remained detectable at in-vivo-like weighting with reduced precision.

neuroscience↗

bioRxiv2026

Longitudinal whole-human-brain quantitative MRI study on autolysis, fixation, rehydration, and shrinkage effects

Postmortem MRI links in vivo MRI contrast to microstructure measured with ex vivo histology, yet fixation systematically alters relevant physical MRI parameters. We quantified these effects by longitudinally characterizing multi-parametric mapping (MPM) measures - longitudinal (R1) and effective transverse (R2*) relaxation rates, normalized proton density proxy (NA), and magnetization transfer saturation (MTsat) - and tissue-volume change in five whole human brains scanned unfixed ex vivo in situ, during formaldehyde immersion fixation, and, when available, after transfer to phosphate buffered saline solution. We included an independent in vivo cohort of 25 younger healthy participants to provide a qualitative in vivo reference. The largest changes were found for R1 during fixation relative to in situ values (up to 351% in dGM), followed by R2* (up to 60% in WM). NA was largely unchanged during fixation. Although MTsat decreased by up to 25% in gray matter from in vivo to in situ, it largely preserved tissue contrast during fixation and PBS immersion, making it an ideal candidate for longitudinal registration across tissue conditions. Phenomenological models characterized fixation-induced parameter changes and relative tissue-volume change. R1 and fixation-associated volume loss evolved under broadly similar timescales, consistent with a contribution from fixation-related water loss or redistribution. This densely sampled dataset and analyses provide a resource for linking in vivo MRI to postmortem fixed-tissue MRI and ex vivo histology under a standardized immersion-fixation protocol.

neuroscience↗

bioRxiv2020

Defective NETs Clearance contributes to sustained FXII Activation in COVID-19-associated Pulmonary Thrombo-Inflammation

BackgroundCoagulopathy and inflammation are hallmarks of Coronavirus disease 2019 (COVID-19) and are associated with increased mortality. Clinical and experimental data have revealed a role for neutrophil extracellular traps (NETs) in COVID-19 disease. The mechanisms that drive thrombo-inflammation in COVID-19 are poorly understood. MethodsWe performed proteomic analysis and immunostaining of postmortem lung tissues from COVID-19 patients and patients with other lung pathologies. We further compared coagulation factor XII (FXII) and DNase activities in plasma samples from COVID-19 patients and healthy control donors and determined NET-induced Factor XIII (FXII) activation using a chromogenic substrate assay. FindingsFXII expression and activity were increased in the lung parenchyma, within the pulmonary vasculature and in fibrin-rich alveolar spaces of postmortem lung tissues from COVID-19 patients. In agreement with this, plasma FXII activation (FXIIa) was increased in samples from COVID-19 patients. Furthermore, FXIIa colocalized with NETs in COVID-19 lung tissue indicating that NETs accumulation leads to FXII contact activation in COVID-19. We further showed that an accumulation of NETs is partially due to impaired NET clearance by extracellular DNases as DNase substitution improved NET dissolution and reduced FXII activation in vitro. InterpretationCollectively, our study supports that the NETs/FXII axis contributes to the pathogenic chain of procoagulant and proinflammatory responses in COVID-19. Targeting both, NETs and FXIIa, could provide a strategy to mitigate COVID-19-induced thrombo-inflammation. FundingThis study was supported by the European Union (840189), the Werner Otto Medical Foundation Hamburg (8/95) and the German Research Foundation (FR4239/1-1, A11/SFB877, B08/SFB841 and P06/KFO306).

molecular biology↗

bioRxiv2020

SARS-CoV-2 infects carotid arteries: implications for vascular disease and organ injury in COVID-19

Stroke and central nervous system dysfunction are cardinal symptoms in critically ill corona virus disease 19 (COVID-19) patients. In an autopsy series of 32 COVID-19 patients, we investigated whether carotid arteries were infected with SARS-CoV-2 by employing genomic, virologic, histochemical and transcriptomic analyses. We show that SARS-CoV-2 productively infects and modulates vascular responses in carotid arteries. This finding has far reaching implications for the understanding and clinical treatment of COVID-19.

microbiology↗